Challenging Cases Edward W. Hook III M.D. Professor and Director Division of Infectious Diseases University of Alabama at Birmingham And PI, Alabama/North Carolina STD PTC
Edward W. Hook, III, M.D. Grant/Research Support: NIH, CDC, WHO, GlaxoSmithKline, Becton Dickinson, Cepheid, Gen-Probe, Roche Molecular, Cempra, Melinta Consultant: Book Editor: Melinta, AstraZeneca, GSK, MedHelp McGraw Hill Speakers Bureau: None
Objectives Determine appropriate therapy for persons with and at risk for STIs reporting medication allergy. Evaluate serologic response to syphilis treatment. Have strategies for evaluating patients with recurrent bacterial vaginosis.
Questions and/or comments from the audience?
Unexpected Results You are asked to see a 19 y.o. college student who was just told that a recent blood test for herpes indicates that she has genital herpes. She is surprised and returns seeking more information.
Unexpected Results (2) The patient tells you tearfully that she is in a serious relationship with another college student and they agreed to be tested before they became sexually active with each other. In your interview you learn: 1 past sexual partner Regular condom use No history of genital lesions or irritation No past STI s (GC, CT, Trich, Syphilis, HIV) History of occasional (once or twice annually) cold sores Possible Explanations? / What Next
Unexpected Results (3) Possible explanations 1. Acquired genital herpes without knowing it 2. Possible false positive result
Unexpected Results (4) Possible explanations 1. Acquired genital herpes without knowing it a) HSV-2 acquired asymptomatically or misidentified -Over half of newly acquired HSV is unrecognized -Younger persons less likely to recognize infection Bernstein, Bellamy, Hook et al. CID 2013; 56: 344-51
Genital Herpes: What People Say They Have Yeast Infections Zipper Cuts Ingrown Hairs Jock Itch Folliculitis Heat Rash UTIs Irritation From: Tight Clothes Bike Seats Vigorous Sex Shaving
Unexpected Results (5) Possible explanations 1. Acquired genital herpes without knowing it a) HSV-2 acquired asymptomatically or misidentified 2. Possible false positive result a) IgM testing b) HSV-1 serological cross reaction
Specificity of Focus HSV-2 ELISA 100 90 80 HSV-1 + in 77% of FP HSV-1 + in 100% of FP 70 % Positive 60 50 40 30 20 10 1.1-1.5 1.5-2.0 2.0-2.5 2.5-3.0 3.0-3.5 >3.5 N= 33 N=33 N=26 N=30 N=20 N=300 Index Value Range Morrow RA, Friedrich D, Meier A, Corey L. BMC Infect Dis 2005; 5:84. 11
Unexpected Results (6) Options For Next Steps 1. Reassurance, no further testing unless lesions develop. 2. Further testing: Western Blot, alternate test (SureCell, Biokit)
Questions and/or comments from the audience?
Recurrent Bacterial Vaginosis Management 24yo female calls you for a prescription. She thinks she has bacterial vaginosis (BV) again because of a recurrence of vaginal discharge and odor. She has had 2 documented BV episodes in the last 3mo (1 st treated with oral flagyl x 7d, 2 nd with flagyl gel vaginally x 5d). She is sexually active. No condom use. Does not douche. What action would you take in terms of need for evaluation, type of treatment, and counseling?
BV Treatment CDC-recommended regimens Metronidazole 500 mg orally twice a day for 7 days or Metronidazole gel 0.75%, one full applicator (5 g) intravaginally, once or twice a day for 5 days or Clindamycin cream 2%, one full applicator (5 g) intravaginally at bedtime for 7 days 15
BV Treatment (continued) Alternative regimens (nonpregnant) Tinidazole 2 g orally once daily for 2 days, or Tinidazole 1 g orally once daily for 5 days, or Clindamycin 300 mg orally twice a day for 7 days, or Clindamycin ovules 100 g intravaginally once at bedtime for 3 days Multiple recurrences Twice weekly metronidazole gel for 4 6 months may reduce recurrences Oral nitroimidazole followed by intravaginal boric acid and suppressive metronidazole gel 16
BV Recurrence Recurrence rate is 20% to 40% one month after therapy. Recurrence may be a result of persistence of BV-associated organisms and a failure of lactobacillus flora to recolonize. Data do not support yogurt therapy or exogenous oral lactobacillus treatment. Under study: vaginal suppositories containing human lactobacillus strains. Twice weekly metronidazole gel for 4 6 months may reduce recurrences. Correct and consistent condom use may reduce recurrences 17
Reverse Sequence Syphilis Testing: Evaluation of EIA+ / RPR- Patients A 32 y.o. woman presents for evaluation of a positive syphilis blood test obtained at her first pre-natal care visit. 8weeks into her first pregnancy GC / CT tests negative No prior STIs EIA + / RPR Does she have syphilis? Should she be treated?
Serologic Tests for Syphilis Nontreponemal Tests (VDRL, RPR) Antigen - cardiolipin-lecithin-cholesterol Quantitative Treponemal Tests (FTA-ABS, MHA-TP, TPPA, EIAs) Treponemal Antigens Qualitative
SYPHILIS SERODIAGNOSIS: Why Use Confirmatory Tests For Screening? Imagine the results of false positive tests (BFPs) when 100,000 people without syphilis are tested. Assume BFP rates of 1.5% for the nontreponemal and 1% for treponemal tests used Screening Non-treponemal Test Treponemal Test 100,000 100,000 x.015 x.01 1500 1000 Confirmatory Testing Treponemal Test Non-treponemal Test 1,500 1,000 x.01 x 0.15 15 15
EIA Serologic Tests for Syphilis EIA= Enzyme Immuno- Assay Pro s Cloned Treponemal Antigens Easy to do in large numbers. Inexpensive Con s Limited data on specificity Positives need quantitative test to assess response to therapy and perhaps for confirmation
MMWR. 2008; 57: 872-875
Reasons For EIA+/RPR- Test Results Past (treated) Syphilis Chronic Untreated Syphilis Very Early Syphilis False Positive
Reverse Sequence Syphilis Testing: Evaluation of EIA + / RPR - Persons Sources of Information on Past Syphilis Tests Prior Pre-Natal Care Blood/Blood Product Donations Prior STI Clinic Visits
Reverse Sequence Syphilis Testing: Evaluation of EIA + / RPR - Persons Evaluation 1. Information on previous testing 2. Thorough H & P 3. Risk Assessment Social / Ecologic Context Likelihood of Follow-up 4. Clinical judgment / patient wishes
Syphilis Response To Treatment A 39 y.o. male returns for follow-up 8 months after treatment for secondary syphilis, at the time of treatment the patient s RPR was reactive at 1:8. His current RPR is positive at 1:4. Does this patient need re-treatment?
Meaningful Change in STS Titers- +/- 2 Dilutions 1:1 1:2 1:4 1:8 1:16 1:32 1:64 1:128 1:256 1:512 Two tube or fourfold dilution decrease 128/4 = 32
Response To Early Syphilis Therapy at 3 Months Following Benzathine Penicillin G or Azithromycin Treatment (n=470) Serological Cure 78.5% (369) Serofast 20.4% (96) Serological Failure 1.1% (5) Hook et al, JID 2010; 201: 1729-35
Recurrent NGU 28yo heterosexual male was treated with doxycycline for NGU 2 weeks prior. His initial chlamydia and GC tests were negative. His urethral symptoms never fully resolved and he now returns for evaluation. NGU is demonstrated again. He reports compliance with treatment and sexual abstinence. What treatment would you give him now? Would you perform any further evaluation? If he does not respond to treatment again, how would you now approach his evaluation and management?